Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors.

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [18F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0". These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.

Hybrid imaging with [68Ga]PSMA-11 PET-CT and PET-MRI in biochemically recurrent prostate cancer.

AIM: To compare [68Ga]PSMA-11 PET-CT, [68Ga]PSMA-11 PET-MRI and MRI in a cohort of prostate cancer (PCa) patients in biochemical recurrence after initial curative therapy. MATERIALS AND METHODS: Fifty-three patients with biochemically recurrent PCa underwent whole-body [68Ga]PSMA-11 PET-CT 1 hour post-injection (p.i.) followed by [68Ga]PSMA-11 PET-MRI 2.5 hours p.i., including a multiparametric MRI pelvic protocol examination. Imaging data analysis consisted of visual (qualitative) evaluation of the PET-CT, PET-MRI and MRI scans, as well as semi-quantitative and quantitative analyses of the PET and MRI data, including calculation of the parameters standardized uptake value (SUV) and apparent diffusion coefficient (ADC) derived from the PCa lesions. Association analysis was performed between imaging and clinical data, including PSA level and Gleason score. The results were considered significant for p-values less than 0.05 (p < 0.05). RESULTS: The hybrid imaging modalities [68Ga]PSMA-11 PET-CT and PET-MRI were positive in more patients than MRI alone. In particular, PET-CT detected lesions suggestive of PCa relapse in 34/53 (64.2%), PET-MRI in 36/53 (67.9%) and MRI in 23/53 patients (43.4%). While no significant differences in lesion detection rate were observed between PET-CT and PET-MRI, the latter was particularly efficient in detection of local recurrences in the prostate bed mainly due to the contribution of the MRI part of the modality. Association analysis revealed a statistically significant increase in the probability of a positive scan with increasing PSA levels for all imaging modalities. Accordingly, there was no significant association between scan positivity rate and Gleason score for any imaging modality. No significant correlation was observed between SUV and ADC values in lymph node metastases. CONCLUSION: [68Ga]PSMA-11 PET-CT and PET-MRI provide equally good detection rates for PCa recurrence, both outperforming stand-alone MRI.

Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0.

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [18F]FDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors. METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard. CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [18F]FDG PET/CT during immunotherapy. Local variations to this guideline should be taken into consideration. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.

Pharmacokinetic studies of [68 Ga]Ga-PSMA-11 in patients with biochemical recurrence of prostate cancer: detection, differences in temporal distribution and kinetic modelling by tissue type.

PURPOSE: [68 Ga]Ga-PSMA-11 is a promising radiopharmaceutical for detecting tumour lesions in prostate cancer, but knowledge of the pharmacokinetics is limited. Dynamic PET-CT was performed to investigate the tumour detection and differences in temporal distribution, as well as in kinetic modelling of [68 Ga]Ga-PSMA-11 by tissue type. METHODS: Dynamic PET-CT over the lower abdomen and static whole-body PET-CT 80-90 min p.i. from 142 patients with biochemical recurrence were retrospectively analysed. Detection rates were compared to PSA levels. Average time-activity curves were calculated from tumour lesions and normal tissue. A three-compartment model and non-compartment model were used to calculate tumour kinetics. RESULTS: Overall detection rate was 70.42%, and in patients with PSA > 0.4 ng/mL 76.67%. All tumour lesions presented the steepest standardised uptake value (SUV) incline in the first 7-8 min before decreasing to different degrees. Normal tissue presented with a low uptake, except for the bladder, which accumulated activity the steepest 15-16 min. p.i.. While all tumour lesions continuously increased, bone metastases showed the steepest decline, resulting in a significantly lower SUV than lymph node metastases (60 and 80-90 min). Transport rate from the blood and tracer binding and internalisation rate were lower in bone metastases. Heterogeneity (fractal dimension) and vascular density were significantly lower in bone metastases. CONCLUSION: Even at low PSA between 0.51 and 0.99 ng/mL, detection rate was 57%. Dynamic imaging showed a time window in the first 10 min where tumour uptake is high, but no bladder activity is measured, aiding accuracy in distinction of local recurrence. Kinetic modelling provided additional information for tumour characterisation by tissue type.

[Periprosthetic fractures of the proximal femur]. / Periprothetische Frakturen des proximalen Femurs.

The incidence of periprosthetic fractures of the proximal femur is increasing due to the growing numbers of hip replacements in old age. The treatment of these fractures is a challenge for the treating physician and standardized procedures are necessary. The unified classification system (UCS) is a suitable tool to establish treatment strategies: On the basis of the fracture localization and extent, bone quality, stability of the prosthesis and the presence of further implants, the fractures can be classified according to the UCS and a treatment algorithm can be derived. This article gives an overview of the diagnostics, classification and characteristics of the various periprosthetic fracture types as well as the treatment.

[Radium-223 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) : The androgen receptor-independent active agent in the therapeutic sequence]. / Radium-223 zur Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) : Der androgenrezeptorunabhängige Wirkstoff in der therapeutischen Sequenz.

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.

18F-PSMA-1007 multiparametric, dynamic PET/CT in biochemical relapse and progression of prostate cancer.

OBJECTIVES: Aim of the present analysis is to investigate the biodistribution and pharmacokinetics of the recently clinically introduced radioligand 18F-PSMA-1007 in patients with biochemical recurrence or progression of prostate cancer (PC) by means of multiparametric (dynamic and whole-body) PET/CT. METHODS: Twenty-five (25) patients with PC biochemical relapse or progression (median age = 66.0 years) were enrolled in the analysis. The median PSA value was 1.2 ng/mL (range = 0.1-237.3 ng/mL) and the median Gleason score was 7 (range = 6-10). All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with 18F-PSMA-1007. PET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and fractal analysis. RESULTS: 15/25 patients were PET-positive. Plasma PSA values in the 18F-PSMA-1007 positive group were higher (median = 3.6 ng/mL; range = 0.2-237.3 ng/mL) than in the 18F-PSMA-1007 negative group (median value = 0.7 ng/mL; range = 0.1-3.0 ng/mL). Semi-quantitative analysis in the PC lesions demonstrated a mean SUVaverage = 25.1 (median = 15.4; range = 3.5-119.2) and a mean SUVmax = 41.5 (median = 25.7; range = 3.8-213.2). Time-activity curves derived from dPET/CT revealed an increasing tracer accumulation during the 60 min of dynamic PET acquisition into the PC lesions, higher than in the urinary bladder and the colon. Significant correlations were observed between 18F-PSMA-1007 uptake (SUV), influx, and fractal dimension (FD). CONCLUSIONS: 18F-PSMA-1007 PET/CT could detect PC lesions in 60% of the patients of a mixed population, including also patients with very low PSA values. Higher PSA values were associated with a higher detection rate. Dynamic PET analysis revealed an increasing tracer uptake during the dynamic PET acquisition as well as high binding and internalization of the radiofluorinated PSMA ligand in the PC lesions.

MRI-based high-precision irradiation in an orthotopic pancreatic tumor mouse model : A treatment planning study.

BACKGROUND AND PURPOSE: Recently, imaging and high-precision irradiation devices for preclinical tumor models have been developed. Image-guided radiation therapy (IGRT) including innovative treatment planning techniques comparable to patient treatment can be achieved in a translational context. The study aims to evaluate magnetic resonance imaging/computed tomography (MRI/CT)-based treatment planning with different treatment techniques for high-precision radiation therapy (RT). MATERIALS AND METHODS: In an orthotopic pancreatic cancer model, MRI/CT-based radiation treatment planning was established. Three irradiation techniques (rotational, 3D multifield, stereotactic) were performed with the SARRP system (Small Animal Radiation Research Platform, Xstrahl Ltd., Camberley, UK). Dose distributions in gross tumor volume (GTV) and organs at risk (OAR) were analyzed for each treatment setting. RESULTS: MRI with high soft tissue contrast improved imaging of GTV and OARs. Therefore MRI-based treatment planning enables precise contouring of GTV and OARs, thus, providing a perfect basis for an improved dose distribution and coverage of the GTV for all advanced radiation techniques. CONCLUSION: An MRI/CT-based treatment planning for high-precision IGRT using different techniques was established in an orthotopic pancreatic tumor model. Advanced radiation techniques allow considering perfect coverage of GTV and sparing of OARs in the preclinical setting and reflect clinical treatment plans of pancreatic cancer patients.

Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.

BACKGROUND: Despite the significant upgrading in recent years of the role of 18F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[18F]fluorothymidine (18F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18F-FLT PET/CT in imaging of MM patients, in the context of its combined use with 18F-FDG PET/CT. RESULTS: Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent 18F-FDG PET/CT and 18F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. 18F-FDG PET/CT demonstrated focal, 18F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, 18F-FLT PET/CT showed focal, 18F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 18F-FDG avid, focal, MM-indicative lesions were detected with 18F-FDG PET/CT, while 17 18F-FLT avid, focal, MM-indicative lesions were detected with 18F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for 18F-FDG PET/CT than for 18F-FLT PET/CT. A common finding was a mismatch of focally increased 18F-FDG uptake and reduced 18F-FLT uptake (lower than the surrounding bone marrow). Moreover, 18F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUVmean and SUVmax were significantly higher for 18F-FLT than for 18F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers. CONCLUSIONS: Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that 18F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

68Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer.

PURPOSE: The aims of this retrospective analysis were to compare 68Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative 68Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases. METHODS: In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with 68Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05. RESULTS: In total, 168 68Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both 68Ga-PSMA PET-positive and CT-positive, 65 were only 68Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more 68Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several 68Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUVaverage and SUVmax), its transport rate from plasma to the interstitial/intracellular compartment (K1), its rate of binding to the PSMA receptor and its internalization (k3), its influx rate (Ki), and its distribution heterogeneity. CONCLUSION: 68Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. 68Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several 68Ga-PSMA PET parameters.

[Response evaluation in nuclear medicine : Criteria, results and pitfalls]. / Nuklearmedizinische Responsebeurteilung : Kriterien, Ergebnisse und Pitfalls.

CLINICAL/METHODICAL ISSUE: Established criteria to categorize metabolic tumor response to cytotoxic chemotherapies may not be suited to capture the effects of therapy with immune checkpoint inhibitors (ICI) or with kinase inhibitors (KI), such as BRAF or MEK inhibitors. NUCLEAR MEDICINE STANDARD METHODS: To assess the metabolic response to cytotoxic chemotherapy by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG), the criteria of the European Organization for Research and Treatment of Cancer (EORTC) and the positron emission tomography response criteria in solid tumors (PERCIST) were conceived. The salient features of both criteria are detailed in a comparative way. PERFORMANCE AND ACHIEVEMENTS: To date only retrospective data exist for the evaluation of therapies with either ICI or KI. They show that response to ICI cannot be reliably determined using the established criteria. Employing the EORTC criteria the responses to KI can be adequately ascertained so that the metabolic tumor response in FDG-PET is regarded as a surrogate marker for the efficacy of these drugs. PRACTICAL RECOMMENDATIONS: Tumor response to therapy with ICI cannot at present be assessed with FDG-PET. Responses to BRAF and MEK inhibitors are, however, assessable using the criteria that were originally developed to evaluate responses to cytotoxic chemotherapy.

[Malignant melanoma : Current status]. / Malignes Melanom : Aktueller Stand.

CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used. As an alternative to CT scans 18 F fluorodeoxyglucose positron emission tomography (FDG-PET) may be used. PERFORMANCE AND ACHIEVEMENTS: Immunotherapy provides the chance of long-term disease control in metastatic melanoma. Ipilimumab may provide long-term tumor control in approximately 20% of patients. Median overall survival of approximately 2 years is achieved during therapy with anti-programmed cell death (PD) 1 antibodies. For combined therapy of ipilimumab and nivolumab a response rate of almost 60% is achieved and 2­year survival is also approximately 60%. The range of immune-mediated side effects demands particular consideration. For response evaluation immune-related response criteria were defined. Furthermore, immunotherapeutic approaches, such as talimogene laherparepvec (T-VEC), which is a modified herpes virus can be used for intralesional injection. PRACTICAL RECOMMENDATIONS: An individual definition of the appropriate therapy for each patient is of particular importance. In the context of modern therapy regimens close patient monitoring is crucial.

Local recurrence of prostate cancer after radical prostatectomy is at risk to be missed in 68Ga-PSMA-11-PET of PET/CT and PET/MRI: comparison with mpMRI integrated in simultaneous PET/MRI.

PURPOSE: The positron emission tomography (PET) tracer 68Ga-PSMA-11, targeting the prostate-specific membrane antigen (PSMA), is rapidly excreted into the urinary tract. This leads to significant radioactivity in the bladder, which may limit the PET-detection of local recurrence (LR) of prostate cancer (PC) after radical prostatectomy (RP), developing in close proximity to the bladder. Here, we analyze if there is additional value of multi-parametric magnetic resonance imaging (mpMRI) compared to the 68Ga-PSMA-11-PET-component of PET/CT or PET/MRI to detect LR. METHODS: One hundred and nineteen patients with biochemical recurrence after prior RP underwent both hybrid 68Ga-PSMA-11-PET/CTlow-dose (1 h p.i.) and -PET/MRI (2-3 h p.i.) including a mpMRI protocol of the prostatic bed. The comparison of both methods was restricted to the abdomen with focus on LR (McNemar). Bladder-LR distance and recurrence size were measured in axial T2w-TSE. A logistic regression was performed to determine the influence of these variables on detectability in 68Ga-PSMA-11-PET. Standardized-uptake-value (SUVmean) quantification of LR was performed. RESULTS: There were 93/119 patients that had at least one pathologic finding. In addition, 18/119 Patients (15.1%) were diagnosed with a LR in mpMRI of PET/MRI but only nine were PET-positive in PET/CT and PET/MRI. This mismatch was statistically significant (p = 0.004). Detection of LR using the PET-component was significantly influenced by proximity to the bladder (p = 0.028). The PET-pattern of LR-uptake was classified into three types (1): separated from bladder; (2): fuses with bladder, and (3): obliterated by bladder). The size of LRs did not affect PET-detectability (p = 0.84), mean size was 1.7 ± 0.69 cm long axis, 1.2 ± 0.46 cm short-axis. SUVmean in nine men was 8.7 ± 3.7 (PET/CT) and 7.0 ± 4.2 (PET/MRI) but could not be quantified in the remaining nine cases (obliterated by bladder). CONCLUSION: The present study demonstrates additional value of hybrid 68Ga-PSMA-11-PET/MRI by gaining complementary diagnostic information compared to the 68Ga-PSMA-11-PET/CTlow-dose for patients with LR of PC.

Long-term outcome of total hip arthroplasty in patients with haemophilia.

INTRODUCTION: Besides the target joints (elbow, knee and ankle), the hip is one of the commonly affected joints in haemophilic arthropathy. Hip arthroplasty is the therapy of choice after failure of conservative treatment. There are only limited data on long-term results after primary total hip arthroplasty (THA). AIM: The aim of this retrospective study was to analyse clinical outcome and complication rate after total hip replacement in patients with severe haemophilic arthropathy. METHODS: Forty-three patients with haemophilia (PWH), one patient with von Willebrand disease and one patient with a Factor-VII-deficiency undergoing 49 total hip arthroplasties, were evaluated in a retrospective study. Harris hip score (HHS), range of motion (ROM), pain status (visual analogue scale, VAS) complication rate and patient satisfaction were assessed at a mean follow-up of 11.5 years (range: 3-32). RESULTS: HSS, ROM and VAS improved significantly combined with high patient satisfaction. In total, three (6.1%) periprosthetic infections and five (10.2%) aseptic implant loosenings occurred after THA leading to revision arthroplasty. In two (4.1%) cases, a pseudotumour and one (2.0%) periarticular ossification had to be resected after THA. CONCLUSION: Total hip replacement in PWH leads to a significant increase of function, reduction of pain and a high satisfaction. Due to the relatively high complication rate (infections and aseptic loosening) compared to patients without haemophilia, an individual assessment of the risk-benefit ratio from surgical and haemostaseological point of view is needed.

Lower limb reconstruction in tumor patients using modular silver-coated megaprostheses with regard to perimegaprosthetic joint infection: a case series, including 100 patients and review of the literature.

PURPOSE AND OBJECTIVE: Bone resection regarding adequate surgical margins is the treatment of choice for malignant bone tumors. In the case of metastasis-related complications, so-called skeletal-related events, it is highly important to achieve pain relief and a stable joint situation to re-mobilize the patients immediately following surgery. To bridge the often large osseous defect zones after tumor resection, both cemented and uncemented modular endoprosthetic systems are widely used. Patients undergoing tumor-related endoprosthetic orthopedic surgery are facing high risk for developing a periprosthetic joint infection (PJI). The immunocompromised condition due to anti-neoplastic treatment and long operation time with large exposure of tissue contributes to a high risk of infection. METHODS: The authors present a case series of 100 patients (31% primary bone tumor and 69% metastasis-related surgery) undergoing tumor-related lower limb salvage surgery with special regard to periprosthetic joint infection and the management of this "difficult to treat" situation. Furthermore, a review of the current literature regarding infection following bone tumor resection and endoprosthetic reconstruction is performed and discussed. RESULTS: The median follow-up was 24 months (range 12-108 months). Ten patients (10%) suffered from a periprosthetic joint infection. We recorded six acute infections (type I) <4 weeks after surgery, one infection >4 weeks after surgery (type II), and three late infections (type III). According to the definition of Laffer et al., three of our patients (30%) are probably free of infection, one patient died of PJI-associated sepsis, and five patients were free of infection, but without restoration of the affected joint. CONCLUSION: In conclusion, our own results show that perimegaprosthetic joint infection among silver-coated implants, in patients undergoing tumor-related surgery of the lower limb, is lower compared to non-silver-coated implants. Due to heterogeneity of patients and potential treatment options, the treatment regime should be tailored for the patients' individual situation.

Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

AIM: The aim of this study was to assess the combined use of the radiotracers 18F-FDG and 18F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). PATIENTS AND METHODS: Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18F-FDG and 18F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). RESULTS: An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18F-FDG PET/CT-based treatment response revealed CR in 14 patients (18F-FDG PET/CT CR), PR in 11 patients (18F-FDG PET/CT PR) and progressive disease in four patients (18F-FDG PET/CT PD). In terms of 18F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18F-NaF PET/CT depicted 56 of the 129 18F-FDG positive lesions (43 %). Follow-up 18F-NaF PET/CT showed persistence of 81.5 % of the baseline 18F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to 18F-FDG negative. Treatment response according to 18F-NaF PET/CT revealed CR in one patient (18F-NaF PET/CT CR), PR in five patients (18F-NaF PET/CT PR), SD in 12 patients (18F-NaF PET/CT SD), and PD in seven patients (18F-NaF PET/CT PD). Dynamic 18F-FDG and 18F-NaF PET/CT studies showed that SUVaverage, SUVmax, as well as the kinetic parameters K1, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p < 0.001). CONCLUSION: F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of 18F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, 18F-NaF PET/CT does not seem to add significantly to 18F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.

[The Role of a Modular Universal Tumour and Revision System (MUTARS®) in Lower Limb Endoprosthetic Revision Surgery - Outcome Analysis of 25 Patients]. / Tumorprothesen in der endoprothetischen Revisionschirurgie der unteren Extremität ­ Ergebnisse von 25 Patienten nach Versorgung mit einem modularen Tumor- und Revisionssystem (MUTARS®).

Introduction/Background: With extended life expectancy, the number of primary joint arthroplasties has also increased. Revision surgery is also more often necessary, due to aseptic or septic loosening of the prosthesis or periprosthetic fracture. Large bone defects often occur in these patients and several non-modular, conventional implants are available to handle this difficult situation. Custom made implants offer an individually designed and defect-adapted shape with perfect covering of the lesion, but may delay the operation. The Modular Universal Tumor And Revision System (MUTARS®) offers the possibility to vary the length and angle of the femoral neck and the antetorsion angle. Thus, it permits intraoperative adaption to the individual patient's defect. The aim of our study is to present clinical, functional results and the rate of complications in a cohort of patients undergoing revision surgery for failed endoprosthetic replacement or failed trauma surgery, using the Modular Universal Tumor And Revision System with short-to midterm follow-up. Patients and Methods: Between August 2005 and September 2014, 25 patients (17 female, 8 male) with an average age of 72 years (min. 56, max. 92 years) were included in a retrospective study using the MUTARS® system. The patients underwent surgical revision of osseous defects that were not susceptible to conventional care. The mean follow-up was 16 months (min. 12, max. 72 months). The indications which led to revision surgery were as follows: loosened metal-on-metal prosthesis with an acetabular defect caused by a metal-induced granuloma (n = 1), pseudoarthrosis after implantation of femur nail (n = 2), cut-out of a femur nail (n = 1), aseptic loosening of an implanted endoprosthesis (n = 4), septic loosening of an implanted endoprosthesis (n = 1), periprosthetic fracture (n = 6) and periprosthetic infection after two stage revision surgery (infection consolidated Girdlestone situation) (n = 10). All patients were followed up at regular intervals, both clinically and radiologically. Apart from comorbidities, clinical and functional parameters were measured, including the Harris Hip Score. An outcome analysis was also performed with respect to peri- and postoperative complications. Serial plain X-rays were followed-up. Results: In all patients, stable reconstruction without the use of an allograft was possible. In total, 23 patients underwent surgery by using a proximal femur prosthesis; three patients also received a custom made acetabular component. One patient was treated by using a distal femur and one patient was treated by implantation of a total femur prosthesis. The average length of hospital stay was 25 days (min.11, max. 47 days). The Harris Hip Score improved from 28 points preoperatively to 81 points after surgery.In total we recorded 24 % of complications after surgery. Two patients suffered recurrent periprosthetic infection and the prosthesis had to be revised in a further two stage exchange; one patient had a tractus gap and was revised by surgery. Two patients suffered periprosthetic fracture due to trauma and the patient with the total femur prosthesis suffered recurrent periprosthetic infection of the silver - coated mega-prosthesis and committed suicide triggered by an episode of major depression. Conclusion: Because of its modular nature, the Modular Tumor And Revision System (MUTARS®) can be used for highly variable intraoperative defect adaption. Good clinical and functional results were achieved in patients with excessive bone defects. However, the high rate of infection, even with silver coated mega-implants, is still a problem and should be studied further.